1. Field of the Invention
This invention relates to a novel process for the synthesis of certain chiral spirofluorenehydantoins, which may be used in the treatment of complications arising from diabetes mellitus. The invention also relates to novel intermediate compounds, which are integral to the claimed process.
2. Description of Related Art
Racemic and the R and S enantiomers of certain chiral spirofluorenehydantoins have previously been reported to be aldose reductase inhibitors and thus of value in controlling complications arising from diabetes mellitus (e.g., diabetic cataracts and neuropathy). Reference is made to commonly assigned U.S. Pat. No. 4,864,028 (York) for further background in this regard. The entire contents U.S. Pat. No. 4,864,028 relating to the utility, structure and synthesis of such chiral spirofluorenehydantoins are hereby incorporated in the present specification by reference.
Methods of obtaining enantiomerically pure forms of chiral hydantoins have been described previously. Prior methods have involved resolution using the resolving agent brucine, or asymmetric synthesis using a method similar to a procedure described in Sarges, et al., J. Orq. Chem., 47:4081 (1982). The present inventors have found that the R and S enantiomers of certain substituted spirofluorenehydantoins, such as 2,7- difluoro-4-methoxyspiro[9H-fluorene-9,4'imidazolidine]-2'5'-dione, cannot be obtained via such prior methods. There is, therefore, a need for a method of synthesizing these enantiomers. The present invention is directed to fulfilling this need. More particularly, the method of this invention provides for the synthesis of the pure R and S enantiomers of the subject compounds.